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Regional and Racial Differences in Drug-Induced Liver Injury

  • Drug-Induced Liver Injury (P Hayashi, Section Editor)
  • Published:
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Abstract

Purpose of Review

To summarize the growing epidemiologic and genetic data that suggest racial and regional differences in drug-induced liver injury (DILI).

Recent Findings

Several registries and population-based studies report incidence data across continents from 2 to 24 per 100,000 with China reporting the highest incidence estimate. The agents causing DILI vary by race and region as well. Hepatotoxicity from herbal and dietary supplement is on the rise globally with China reporting the highest levels. Genome-wide association studies are beginning to shed light on racial genetic and HLA variants which may determine the risk of DILI.

Summary

DILI risk and outcome vary by race and region due to a combination of epidemiologic and genetic factors. The rise and maturation of DILI registries worldwide are beginning to allow important discoveries in how we should consider the diagnosis of DILI by region and race.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. • Shen T, Liu Y, Shang J, et al. Incidence and etiology of drug-induced liver injury in mainland China. Gastroenterology. 2019;156(8):2230–41. Largest population-based study on DILI to date and only one focusing on predominantly non-Caucasians .

  2. Takikawa H, Murata Y, Horiike N, Fukui H, Onji M. Drug-induced liver injury in Japan: an analysis of 1676 cases between 1997 and 2006. Hepatol Res. 2009;39(5):427–31.

    Article  Google Scholar 

  3. Devarbhavi H, Dierkhising R, Kremers WK, Sandeep MS, Karanth D, Adarsh CK. Single-center experience with drug-induced liver injury from India: causes, outcome, prognosis, and predictors of mortality. Am J Gastroenterol. 2010;105(11):2396–404.

    Article  Google Scholar 

  4. Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, et al. Features and outcomes of 899 patients with drug-induced liver injury: the DILIN prospective study. Gastroenterology. 2015;148(7):1340–52 e1347.

    Article  Google Scholar 

  5. Vega M, Verma M, Beswick D, et al. The incidence of drug- and herbal and dietary supplement-induced liver injury: preliminary findings from gastroenterologist-based surveillance in the population of the state of Delaware. Drug Saf. 2017;40(9):783–7.

    Article  CAS  Google Scholar 

  6. Bjornsson ES, Bergmann OM, Bjornsson HK, Kvaran RB, Olafsson S. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013;144(7):1419–25 1425 e1411–1413; quiz e1419–1420.

    Article  Google Scholar 

  7. Sgro C, Clinard F, Ouazir K, Chanay H, Allard C, Guilleminet C, et al. Incidence of drug-induced hepatic injuries: a French population-based study. Hepatology. 2002;36(2):451–5.

    Article  Google Scholar 

  8. Andrade RJ, Lucena MI, Fernandez MC, et al. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology. 2005;129(2):512–21.

    Article  Google Scholar 

  9. Bjornsson E, Olsson R. Outcome and prognostic markers in severe drug-induced liver disease. Hepatology. 2005;42(2):481–9.

    Article  Google Scholar 

  10. Bjornsson E, Olsson R. Suspected drug-induced liver fatalities reported to the WHO database. Dig Liver Dis. 2006;38(1):33–8.

    Article  CAS  Google Scholar 

  11. Danan G, Benichou C. Causality assessment of adverse reactions to drugs--I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol. 1993;46(11):1323–30.

    Article  CAS  Google Scholar 

  12. • Medina-Caliz I, Garcia-Cortes M, Gonzalez-Jimenez A, Cabello MR, Robles-Diaz M, Sanabria-Cabrera J, et al. Herbal and dietary supplement-induced liver injuries in the Spanish DILI registry. Clin Gastroenterol Hepatol. 2018;16(9):1495–502. Registry data suggesting a rise in DILI due to herbal and dietary supplements in Spain.

    Article  Google Scholar 

  13. Navarro VJ, Barnhart H, Bonkovsky HL, Davern T, Fontana RJ, Grant L, et al. Liver injury from herbals and dietary supplements in the U.S. drug-induced liver injury network. Hepatology. 2014;60(4):1399–408.

    Article  Google Scholar 

  14. Robles-Diaz M, Gonzalez-Jimenez A, Medina-Caliz I, Stephens C, García-Cortes M, García-Muñoz B, et al. Distinct phenotype of hepatotoxicity associated with illicit use of anabolic androgenic steroids. Aliment Pharmacol Ther. 2015;41(1):116–25.

    Article  CAS  Google Scholar 

  15. • Stolz A, Navarro V, Hayashi PH, et al. Severe and protracted cholestasis in 44 young men taking bodybuilding supplements: assessment of genetic, clinical and chemical risk factors. Aliment Pharmacol Ther. 2019;49(9):1195–204. Good clinical description of liver injury due to body-building supplements .

    Article  CAS  Google Scholar 

  16. •• Chalasani N, Reddy KRK, Fontana RJ, et al. Idiosyncratic drug induced liver injury in African-Americans is associated with greater morbidity and mortality compared to Caucasians. Am J Gastroenterol. 2017;112(9):1382–8. The first study to identify differences in DILI risk and outcome in US African-Americans .

    Article  CAS  Google Scholar 

  17. Hayashi PH, Bjornsson ES. Long-term outcomes after drug-induced liver injury. Curr Hepatol Rep. 2018;17(3):292–9.

    Article  Google Scholar 

  18. Hayashi PH, Rockey DC, Fontana RJ, Tillmann HL, Kaplowitz N, Barnhart HX, et al. Death and liver transplantation within 2 years of onset of drug-induced liver injury. Hepatology. 2017;66(4):1275–85.

    Article  CAS  Google Scholar 

  19. Zimmerman HJ. Drug-induce liver injury. In: Zimmerman HJ, editor. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lipponcott Williams & Wilkins; 1999. p. 432–3.

    Google Scholar 

  20. Robles-Diaz M, Lucena MI, Kaplowitz N, Stephens C, Medina-Cáliz I, González-Jimenez A, et al. Use of Hy’s law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury. Gastroenterology. 2014;147(1):109–118 e105.

    Article  CAS  Google Scholar 

  21. Chalasani N, Bjornsson E. Risk factors for idiosyncratic drug-induced liver injury. Gastroenterology. 2010;138(7):2246–59.

    Article  CAS  Google Scholar 

  22. Satapathy SK, Sanyal AJ. Epidemiology and natural history of nonalcoholic fatty liver disease. Semin Liver Dis. 2015;35(3):221–35.

    Article  Google Scholar 

  23. Liu CJ, Kao JH. Global perspective on the natural history of chronic hepatitis B: role of hepatitis B virus genotypes A to J. Semin Liver Dis. 2013;33(2):97–102.

    Article  Google Scholar 

  24. Hwang SJ, Wu JC, Lee CN, et al. A prospective clinical study of isoniazid-rifampicin-pyrazinamide-induced liver injury in an area endemic for hepatitis B. J Gastroenterol Hepatol. 1997;12(1):87–91.

    Article  CAS  Google Scholar 

  25. Saha A, Shanthi FXM, Winston AB, et al. Prevalence of hepatotoxicity from antituberculosis therapy: a five-year experience from South India. J Prim Care Community Health. 2016;7(3):171–4.

    Article  Google Scholar 

  26. Patel PA, Voigt MD. Prevalence and interaction of hepatitis B and latent tuberculosis in Vietnamese immigrants to the United States. Am J Gastroenterol. 2002;97(5):1198–203.

    Article  Google Scholar 

  27. Wong WM, Wu PC, Yuen MF, Cheng CC, Yew WW, Wong PC, et al. Antituberculosis drug-related liver dysfunction in chronic hepatitis B infection. Hepatology. 2000;31(1):201–6.

    Article  CAS  Google Scholar 

  28. Lee BH, Koh WJ, Choi MS, et al. Inactive hepatitis B surface antigen carrier state and hepatotoxicity during antituberculosis chemotherapy. Chest. 2005;127(4):1304–11.

    CAS  PubMed  Google Scholar 

  29. Wang NT, Huang YS, Lin MH, Huang B, Perng CL, Lin HC. Chronic hepatitis B infection and risk of antituberculosis drug-induced liver injury: systematic review and meta-analysis. J Chin Med Assoc. 2016;79(7):368–74.

    Article  Google Scholar 

  30. Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, et al. Epidemiological serosurvey of hepatitis B in China--declining HBV prevalence due to hepatitis B vaccination. Vaccine. 2009;27(47):6550–7.

    Article  Google Scholar 

  31. Bessone F, Dirchwolf M, Rodil MA, Razori MV, Roma MG. Review article: drug-induced liver injury in the context of nonalcoholic fatty liver disease - a physiopathological and clinical integrated view. Aliment Pharmacol Ther. 2018;48(9):892–913.

    Article  CAS  Google Scholar 

  32. •• Lammert C, Imler T, Teal E, Chalasani N. Patients with chronic liver disease suggestive of nonalcoholic fatty liver disease may be at higher risk for drug-induced liver injury. Clin Gastroenterol Hepatol. 2018. https://doi.org/10.1016/j.cgh.2018.12.013. Early data suggesting an increase risk of DILI in those with NAFLD.

  33. Tarantino G, Conca P, Basile V, Gentile A, Capone D, Polichetti G, et al. A prospective study of acute drug-induced liver injury in patients suffering from non-alcoholic fatty liver disease. Hepatol Res. 2007;37(6):410–5.

    Article  CAS  Google Scholar 

  34. Wong MCS, Huang JLW, George J, Huang J, Leung C, Eslam M, et al. The changing epidemiology of liver diseases in the Asia-Pacific region. Nat Rev Gastroenterol Hepatol. 2019;16(1):57–73.

    Article  Google Scholar 

  35. Daly AK, Donaldson PT, Bhatnagar P, et al. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet. 2009;41(7):816–9.

    Article  CAS  Google Scholar 

  36. Lucena MI, Molokhia M, Shen Y, Urban TJ, Aithal GP, Andrade RJ, et al. Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles. Gastroenterology. 2011;141(1):338–47.

    Article  CAS  Google Scholar 

  37. Middleton D, Menchaca L, Rood H, Komerofsky R. New allele frequency database: http://www.allelefrequencies.net. Tissue Antigens. 2003;61(5):403–7.

    Article  CAS  Google Scholar 

  38. •• Maiers M, Gragert L, Klitz W. High-resolution HLA alleles and haplotypes in the United States population. Hum Immunol. 2007;68(9):779–88.

    Article  CAS  Google Scholar 

  39. Cirulli ET, Nicoletti P, Abramson K, et al. A missense variant in PTPN22 is a risk factor for drug-induced liver injury. Gastroenterology. 2019;156(6):1707–1716 e1702. Important study identifying a genetic mutation that has variable prevalence across populations and when linked to certain HLA mutations may substantially increase the risk of DILI for certain medications .

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, University of North Carolina Liver Center, Burnett-Womack Building, Room 8011, Chapel Hill, NC, 27599, USA

    Paul H. Hayashi

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This article is part of the Topical Collection on Drug-Induced Liver Injury

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Hayashi, P.H. Regional and Racial Differences in Drug-Induced Liver Injury. Curr Hepatology Rep 18, 280–286 (2019). https://doi.org/10.1007/s11901-019-00476-y

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